Hard and soft capsules are frequently preferred by patients as a dosage form. In hard and soft capsules, the drug-fill is contained within the capsule shell, resulting in a generally tasteless and odorless delivery system. In addition, many patients find it easier to swallow capsules than other oral dosage forms, such as tablets.
From the formulator's point of view, hard and soft capsules provide capabilities and options for dosage form design and formulation. For instance, hard capsules do not require the design of a compact capable of withstanding the handling required to produce a compressed tablet. In some cases, it is possible to direct-fill capsules with agents that otherwise require complex granulation procedures to be tableted. In addition, modern capsule-filling machines allow hard capsules to be filled with beads, granules, tablets, powders, and pumpable liquids. This capability provides the formulator with numerous options for designing delivery systems, or simply for separating incompatible substances within a single capsule.
Similarly, soft capsules are an attractive dosage form. In particular, soft capsules are useful for delivering many liquid formulations, including suspensions and pastes. Liquid ingredients are difficult to include in any other solid dosage form (e.g., as a tablet). Therefore, soft capsules are the exclusive means of formulating many liquid active pharmaceutical ingredients (APIs), including valproic acid, benzonatate, and oils, such as fish oil. Soft capsules are also particularly well suited for formulating many potent APIs (for example, where the dose is <100 μg). The highly reproducible filling process helps ensure each soft capsule contains the same dosage of API. In addition, soft capsules can be prepared under mild conditions. As a result, they are attractive for delivering, for example, temperature-sensitive active agents.
Despite their many advantages, existing hard and soft capsules are not compatible with all types of pharmaceutical formulations. For example, many active pharmaceutical ingredients (APIs) which have poor bioavailability (e.g., APIs classified as Class IV under the Biopharmaceutical Classification System (BCS)) require self-emulsifying drug delivery systems (SEDDS) or self-microemulsifying drug delivery systems (SMEDDS) which employ polyethoxylated surfactants. Many existing soft capsule shells are not compatible with high HLB-value surfactants. In particular, high-HLB-value surfactants can weaken the seams of soft capsules, resulting in fill leakage over time.
In addition, many controlled release formulations employ high melting point waxes that bind the API and provide the desired sustained release profile. The encapsulation of such formulations in existing soft capsules is problematic because the makeup of existing soft capsules requires that encapsulation be conducted in a narrow temperature range. Above this temperature range, the viscosity of the gel mass becomes too low to reliably form soft capsules with suitable stability (e.g., having properly sealed seams).
Further, enteric dosage forms are useful for protecting the contents of a dosage form from the gastric conditions of the stomach and/or to protect gastric tissue from an irritant material contained in the dosage form. Enteric-coated dosage forms are typically produced by a film coating process, where a thin film layer of an acid-insoluble (enteric) polymer is applied to the surface of a pre-manufactured dosage form. However, the enteric coating of conventional hard and capsules is problematic. Both hard and soft capsules can undergo thermally induced agglomeration and distortion of the capsule shell during coating. Moreover, the smoothness and elasticity of the capsule surface makes it difficult to form an intact adhering enteric coating, without a subcoating step to improve the surface of the capsule for coating. Finally, the enteric coatings cause the loss of the normally shiny and clear appearance of many capsule shells, which is a major reason for their popularity and acceptance.